Up-regulation of Adiponectin by Resveratrol

• DOI: 10.1074/jbc.m110.188144
• Publication Date: 2010-10-28T00:17:39Z
• Authors: Anping Wang; Meilian Liu; Xianling Liu; Lily Q. Dong; Randolph D. Glickman; Thomas J. Slaga; Zhiguang Zhou; Feng Liu
• Keywords: 0301 basic medicine; Forkhead Box Protein O1; Pyruvate Dehydrogenase Acetyl-Transferring Kinase; Forkhead Transcription Factors; AMP-Activated Protein Kinases; Protein Serine-Threonine Kinases; Up-Regulation; Mice; 03 medical and health sciences; Resveratrol; 3T3-L1 Cells; Stilbenes; Adipocytes; Animals; RNA Interference; Adiponectin; RNA, Messenger; Protein Multimerization; Protein Structure, Quaternary; Proto-Oncogene Proteins c-akt; Glutathione Transferase; Signal Transduction

The natural polyphenol resveratrol (RSV) displays a wide spectrum of health beneficial activities, yet the precise mechanisms remain to be fully elucidated. Here we show that RSV promotes the multimerization and cellular levels of adiponectin in 3T3-L1 adipocytes. The stimulatory effect of RSV was not affected by knocking out Sirt1, but was diminished by suppressing the expression levels of DsbA-L, a recently identified adiponectin-interactive protein that promotes adiponectin multimerization. Suppression of the Akt signaling pathway resulted in an increase in the expression levels of DsbA-L and adiponectin. On the other hand, knocking out FOXO1 or suppressing the activity or expression levels of the AMP-activated protein kinase (AMPK) down-regulated DsbA-L and adiponectin. The stimulatory effect of RSV on adiponectin and DsbA-L expression was completely diminished in FOXO1-suppressed and AMPK-inactivated 3T3-L1 adipocytes. Taken together, our results demonstrate that RSV promotes adiponectin multimerization in 3T3-L1 adipocytes via a Sirt1-independent mechanism. In addition, we show that the stimulatory effect of RSV is regulated by both the Akt/FOXO1 and the AMPK signaling pathways. Last, we show that DsbA-L plays a critical role in the promoting effect of RSV on adiponectin multimerization and cellular levels.